The central goal of this project is to define, at the level of nucleotide sequences of the genes, the mutations that cause various forms of epidermolysis bullosa (EB) and other disorders affecting the epidermis. The emphasis on this project in the past four years has been on elucidation of mutations in the well-established forms of EB, viz. the classic dystrophic (DEB) and junctional forms (JEB). During this past project period, since 1996, we have analyzed a total of 368 families with different forms of EB; for mutations in the candidate genes. As a result of these efforts, we have been able to identify 136 distinct mutations in the We VII collagen gene (CQL7A 0 in families with various forms of DEB, and examination of the mutation database has allowed us to develop genotype/phenotype correlations with prognostic implications (see the Progress Report below). Similarly, we have examined a total of 132 families with different forms of JEB, and we have been able to identify 118 distinct-mutations in six different genes underlying different variants of JEB, these include LAMA3, LAMB3, LAMC2, ITGB4, ITGA6, and BPAG2/COL17Al. Within each JEB subtype, there is considerable phenotypic variability, and careful examination of the mutation database has allowed us to identify certain genotype/phenotype correlations. Thus, collectively, there has been a tremendous progress in elucidating the underlying molecular basis of different forms of EB.